More than 90% of human deaths resulting from mushroom poisoning are due to peptide toxins found in Amanita species of mushrooms, such as A. phalloides, A. bisporigera, A. ocreata, and A. virosa. Animals, especially dogs, are frequent victims of poisoning by Amanita mushrooms. Two dogs died after eating toxin containing mushrooms in Michigan, See Schneider: Mushroom in backyard kills curious puppy, Lansing State Journal, Sep. 30, 2008. Besides species in the genus Amanita, other genera of mushrooms make similar toxins, such as phallotoxins and amatoxins. These other genera include Galerina, Conocybe, and Lepiota. Poisonings due to Galerina species have occurred, see FIG. 31.
High concentrations of peptide toxins are found in the above ground mushroom portion (otherwise known as carpophores or fruiting bodies) of the toxin producing mushroom species. These toxins include two major families of compounds called amatoxins (for example, α-amanitin. FIG. 1A) and phallotoxins (for example, phalloidin, phallacidin, FIG. 1B). Both classes of compounds are bicyclic peptides with a Cys-Trp cross-bridge. In general, amatoxins are 8 amino acids in length while phallotoxins are 7 amino acids in length. Amatoxins are produced by Amanita and some Galerina species of mushrooms. Galerina species in general do not make phallotoxins. Amatoxins survive cooking and remain intact in the intestinal tract where they are absorbed into the body where large doses irreversibly damage the liver and other organs (Enjalbert et al., (2002) J. Toxicol. Clin. Toxicol. 40:715; herein incorporated by reference).
Amatoxins and phallotoxins are used extensively for experimental research. Amatoxins are a family of bicyclic peptides that inhibit RNA polymerase II while phallotoxins bind and stabilize F-actin. However Amanita species do not grow well in the laboratory and harvesting from wild sources limits availability of a natural source of these peptides.
Thus it would be useful to have methods for obtaining large quantities of bicyclic amatoxins in addition to custom designed bicyclic amatoxin and phallotoxin peptides using cultivatable mushrooms.